• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• Journal of Food Hygiene and Safety
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• v.15 no.2
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• pp.122-127
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• 2000

An antifungal bacterium was isolated to inhibit of the growth of Asp. flavus and Asp. parasiticus, and its antifungal compounds were purified from lyophilized culture broth using chromatographic methods. Antifungal bacterium #19 which was shown a higher inhibitory activity on the growth of aflatoxin producing fungi was identified as Bacillus subtilis. The purified antifungal compound(1 mg) was demonstrated strong antifungal activity against the aflatoxin producing fungi.

• Korean Journal of Clinical Pharmacy
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• v.34 no.1
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• pp.71-78
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• 2024

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience. However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA provides some guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted to understand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions: Study finds TKI-DDI not significantly linked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

• Korean Journal of Pharmacognosy
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• v.5 no.3
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• pp.147-154
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• 1974

Some crude drugs in ancient literatures have been used as traditional therapeutic agent of leucorrhea mainly caused by Trichomonas vaginalis and Candida albicans. Sixty six kinds of crude drugs in ancient literatures and ten constituents were selected as sample drugs. Trichomycin standard was tested to compare with the above drugs. To determine the anti-fungal effect of these drugs on Candida albicans Yu 1200, a test organism, screening test was conducted. Antifungal activities of crude drug water extracts were observed by means of two test methods : firstly through the agar slant method and secondly the counting chamber method which was used for acknowledged drug agents upon the result of the agar slant method. And in order to improve the fungicidal effect, the organisms were stained with 0.02% methylene blue solution. The results of the above test indicated that Fritillariae Rhizoma has antifungal action in the concentration of 310mcg/ml, Coptidis Rhizoma in 620mcg/ml, Meliae Cortex, Scutellariae Radix both in 5,000mcg/ml. Baicalin, catechol among the pure isolated constituents inhibited in the range of 50mcg/ml. This score was based on 50% inhibition in comparison with amounts of control organisms. Rhei Rhizoma, Mori Radicis Cortex, Linderae Radix, and Amomi globosi Fructus showed the antifungal effect moderately in 5,000mcg/ml, and baicalein and pectolinarin in 50mcg/ml in the limit of between 35% and 50% antifungal activity. Staining with 0.02% methylene blue showed that any of the crude drug extracts was unable to stain the cells, but trichomycin in 0.86unit/ml able to stain 12% of the cells. This result means that crude drugs probably do not have fungicidal but fungistatic action.

• Journal of Microbiology and Biotechnology
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• v.33 no.2
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• pp.180-187
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• 2023

The skin is a dynamic ecosystem on which diverse microbes reside. The interkingdom interaction between microbial species in the skin microbiota is thought to influence the health and disease of the skin although the roles of the intra- and interkingdom interactions remain to be elucidated. In this context, the interactions between Malassezia and Staphylococcus, the most dominant microorganisms in the skin microbiota, have gained attention. This study investigated how the interaction between Malassezia and Staphylococcus affected the antifungal susceptibility of the fungus to the azole antifungal drug ketoconazole. The susceptibility was significantly decreased when Malassezia was co-cultured with Staphylococcus. We found that acidification of the environment by organic acids produced by Staphylococcus influenced the decrease of the ketoconazole susceptibility of M. restricta in the co-culturing condition. Furthermore, our data demonstrated that the significant increased ergosterol content and cell membrane and wall thickness of the M. restricta cells grown in the acidic environment may be the main cause of the altered azole susceptibility of the fungus. Overall, our study suggests that the interaction between Malassezia and Staphylococcus influences the antifungal susceptibility of the fungus and that pH has a critical role in the polymicrobial interaction in the skin environment.

• Journal of Applied Biological Chemistry
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• v.55 no.1
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• pp.7-11
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• 2012

The antifungal activities of the bee venom against Trichophyton mentagrophytes and Trichophyton rubrum were determined by using modified broth dilution assay. The most common dermatophytes, named T. mentagrophytes and T. rubrum, were known to cause a variety of cutaneous infections in humans and animals. The bee venom exhibited prominent antifungal activities against the two dermatophytes tested in this investigation. Moreover, the antifungal activities of the bee venom were much stronger than that of fluconazole, one of the commercial antifungal drugs used in the treatment and prevention of superficial and systemic fungal infections. The result suggests that bee venom could be developed as a natural antifungal drug.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.234-247
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• 2021

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

• CELLMED
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• v.6 no.4
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• pp.22.1-22.19
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• 2016

The biologically active compounds derived from different natural organisms such as animals, plants, and microorganisms like algae, fungi, bacteria and merine organisms. These natural compounds possess diverse biological activities like anthelmintic, antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antiviral activities. These biological active compounds were acted by variety of molecular targets and thus may potentially contribute to several pharmacological classes. The synthesis of natural products and their analogues provides effect of structural modifications on the parent compounds which may be useful in the discovery of potential new drug molecules with different biological activities. Natural organisms have developed complex chemical defense systems by repelling or killing predators, such as insects, microorganisms, animals etc. These defense systems have the ability to produce large numbers of diverse compounds which can be used as new drugs. Thus, research on natural products for novel therapeutic agents with broad spectrum activities and will continue to provide important new drug molecules.